Periodontitis is a bacterially induced inflammatory disorder of the tooth-supporting structures that is associated with elevated systemic inflammation. Its prevalence increases significantly with age and is particularly elevated in minority and disadvantaged populations. Limited evidence suggests that poor oral health is associated with prevalent cognitive impairment and incident dementia, but the effect of periodontitis on cognitive aging and dementia has not been examined in detail. In this proposal, we intend to formally test the hypothesis that periodontitis is an unrecognized risk factor for incident cognitive impairment among the participants in the WHICAP cohort currently being enrolled. WHICAP is a multi-ethnic longitudinal cohort of aging elderly residing in northern Manhattan. Since its inception nearly 20 years ago, more than 4,000 participants have been serially assessed in 24-month intervals with medical, social, and health behavior histories, general medical exams, and neuropsychological testing. To date, analyses of WHICAP data have markedly increased our knowledge of the complex influence of sociodemographics, genetics, health behavior and lifestyle, education, literacy, and vascular disease in the expression of incident AD and cognitive decline. In addition to these measures, current WHICAP participants are also being assessed for multiple AD biomarkers including multimodal MRI, amyloid-labeled brain positron emission tomography (amyloid-PET), and plasma amyloid. We propose to perform a detailed assessment of periodontal status using clinical, microbiological and serological markers and prospectively explore the role of periodontitis as an independent risk factor for incident AD and cognitive decline over a 4-year period. Furthermore, we will repeat the same assessments of periodontal status at 24 months after baseline, and will examine the association between the deterioration of periodontal status over the first 2-year period and incident cognitive decline over the subsequent 2-year period. We will also assess prospectively the association between microbial and serological markers of periodontitis and biomarkers of cognitive decline. Incorporating assessments of periodontal infection within the WHICAP study provides a unique opportunity to explore efficiently how periodontitis may relate to conventional measures of cognitive aging (such as neurologic and neuropsychological examinations) but also to explore sub-clinical associations among biomarkers of both diseases. Given the substantial unexplained variance in AD and dementia in the elderly population and the fact that periodontitis is both preventable and treatable, identification of periodontitis as a potential unrecognized risk factor/marker for cognitive impairment will be extremely valuable from a public health standpoint.